Inhibition of tubulin polymerization is the target of many antitumoural agents known as antimitotic agents or spindle poisons colchicines, podophyllo-toxins and combretastatins are representative examples of compounds that inhibit microtubule assembly by binding to tubulin. 2-Aryl- and 2-styrylquinazolin-4(3H)-ones (SQZ) and 2,3-dihydro-2-aryl-4-quinazolinones (DHPQ) are compounds that possess this common structural feature for an effective interaction with tubulin. The antitumor activities of 2,3-dihydro-2-aryl-4-quinazolinones (DHPQZ) were reported around 1970 (Yale H L, Kalkstein M. Substituted 2,3-dihydro-4(1H)-quinazolinones, a new class of inhibitors_of cell multiplication. J Med Chem 1967 10, 334-336, Neil, G. L.; Li, L. H.; Buskirk, H. H.; Moxlcy, T. E. Cancer Chemother. 1972, 56, 163-173. and Hamel, E.; Lin, C. M.; Plowman, J.; Wang, H. K.; Lee, K. H.; Paull, K. D. Antitumor 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone derivatives. Interactions with tubulin. Biochem. Pharmacol. 1996, 51, 53-59). A more recent reevaluation of this type of compound by NCI against human tumor cell lines reconfirmed that, like colchicine, they are effective inhibitors of tubulin polymerization. Many isoxazole, isoxazoline type moieties related to combretastain A-4 showed potential biological properties particularly anticancer activity (Simoni, D.; Grisolia, G.; Giannini, G.; Roberti, M.; Rondanin, R.; Piccagli, L.; Baruchello, R.; Rossi, M.; Romagnoli, R.; Invidiata, F. P.; Grimaudo, S.; Jung, M. K.; Hamel, E.; Gebbia, N.; Crosta, L.; Abbadessa, V.; DiCristina, A.; Dusonchet, L.; Meli, M.; Tolomeo, M. J. Med. Chem. 2005, 48, 723, Julia Kaffy, a Renée Pontikis,a,* Danièle Carrez,b Alain Croisy, Claude Monnereta and Jean-Claude Florent. Bioorg. Med. Chem. 2006, 14, 4067-4077, Gian Ceasure Tron, Tracy Pirali, Giovanni sorba, Francesca pagliai, Sara Buasacca and Armado A. Genazzani. J. Med. Chem. 2006, 49, 3033-3044. and Tracey Pirali, Sara buasacca, Lorena Beltrami, Daniela Imovilli, Francesca Paliai, Gianluca Migilio, Alberto Massrotti, Luisella Verotta, Gian Cesare Tron, Givanni Sorba, and Armado A. Genazzani. J. Med. Chem. 2006, 49, 5372-5376). Some of the heterocyclic bridged Combretastains showed an attractive profile cytotoxicity and were able to induce apoptosis at lower concentrations.
